The invention relates to a process for the production of pseudolatices and micro- or nanoparticles, their use and pharmaceutical preparations containing such pseudolatices or micro- or nanoparticles.
Usually, systems described as pseudolatices are those which are obtained by emulsifying organic polymer solutions in water and removing the solvents (G. S. Banker, G. E. Peck, Pharm. Technol. 5 (1981)). The recent production of pseudolatices is therefore mainly based on a corresponding process which was developed especially for cellulose derivatives (A. M. Ortega, dissertation, Purdue University, West Lafayette (USA) (1977)).
In view of the toxicity, the costs and the environmentally-damaging character of organic solvents, it was attempted to avoid processing polymers in such organic solvents.
For this reason, disperse, aqueous systems of some polymers were developed in the past, for example of cellulose derivatives and polymethacrylates.
Various routes were followed for this:
Development of emulsion polymerisates based on methacrylate (K. Lehmann, D. Dreher, Pharm. Ind. 34, 894 (1972)). PA1 Partial replacement of organic solvents in aqueous organic plastics emulsions (K. H. Bauer, H. Osterwald, Pharm. Ind. 41, 1203 (1979)). PA1 Use of plastics dispersions together with auxiliaries soluble in water or in alkali (W. Rohte, G. Groppenbacher, Pharm. Ind. 34, 892 (1972)). PA1 Emulsification in organic solvents of dissolved cellulose derivatives in water and removal of the solvents (A. M. Ortega, dissertation, Purdue University, West Lafayette (USA) (1977)). PA1 Direct emulsification of hydrophilic methacrylates in water (K. Lehmann, Acta Pharm. Technol. 32, 146 (1986)). PA1 Dispersion of micronised polymers in aqueous solutions of plasticizers and film-coating at higher temperatures by thermal alloying (K. H. Bauer, H. Osterwald, Acta Pharm. Technol. 27, 99 (1986)). PA1 Use of the aqueous solutions of salts of anionic polymerisates using volatile bases (K. H. Fromming, K. P. Krahl, Pharm. Ind. 43, 863 (1981)) or post-treating with acids (U.S. Pat. No. 4,017,647).
At low temperatures polymers are often hard, rigid solids. On heating, the polymer material receives enough thermal energy for its chains to be able to move. Above the melting temperature, the polymer behaves like a viscous liquid (provided there is no degradation). In the transition from the solid vitreous state to the liquid state, various intermediate states are passed through.
With crystalline polymers, an equilibrium between the solid and liquid states exists at the melting point. With crystalline substances, the molecular movement at the melting point rises rapidly from a relatively low level to a high level. In contrast, amorphous polymers behave differently. The molecular movement here increases slowly in several stages with increasing temperature. In contrast to crystalline polymers, in the case of amorphous or partially crystalline polymers not two, but several, different transition temperature ranges are to be noted. There are often 5 viscoelasticity ranges, e.g. in the case of polystyrene (J. M. G. Cowie, Chemie und Physik der Polymeren, Verlag Chemie (1976)).
The temperature at which a polymer changes from the vitreous state into the elastic state is called the glass transition temperature. A much-used method for determining the glass transition temperature is differential thermal analysis (DSC method) (W. C. Stanger, J. K. Guillory, J. Pharm. Sci. 68, 1005 (1979)).